Detailed studies on the pharmacokinetics, i.e., absorption, distribution, tissue and plasma binding, and excretion; and biotransformation, i.e., metabolism of Phase I, II, and III, and adjuvant anticancer drugs in animals and man will be initiated and integrated with present Central Oncology Group (COG) clinical studies. The chemical and physical properties of these drugs will be investigated prior to the development of appropriate, sensitive, quantitative analytical methods applicable to in vivo and in vitro biological systems. These methods will be employed in studies of the rate of drug metabolism and excretion, and will be used to isolate and characterize the products of metabolism by animals and human subjects. The antitumor pharmacologic activity of identified drug metabolites will be investigated. Studies of the biopharmaceutics of selected drugs demonstrating human antineoplastic activity will be conducted. Drug protocol studies proposed for human investigation by collaborating members of the COG will be reviewed from a pharmacologic standpoint prior to final submission. Newly developed animal solid tumor models, e.g., intestine and large bowel, urinary bladder, kidney, stomach, breast, lung, etc., will be employed to test specific drug protocols, proposed by the COG, prior to initiation of human trials. Correlates and in vivo predictors of possible human sensitivity to specific carcinogen-induced solid tumors will be sought through the animal models, in an effort to develop effectiveness data on the most probably effective of all possible multiple antineoplastic drug combinations. These efforts will be directed toward the goal of developing the most advantageous clinical utilization of current and new drugs in solid tumor chemotherapy.